Hydrochloric Acid → phenylmethyl [2-(4-amino-3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-7-yl)ethyl]carbamate

HRID 1910029

Reaction equation

HRID 1910029 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([N:43](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:27][CH:28]=[C:29]([CH2:30][CH2:31][NH:32][C:33]([O:35][CH2:36][C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)=[O:34])[C:24]=4[O:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11].Cl.O1CCOCC1>>[C:37]1([CH2:36][O:35][C:33](=[O:34])[NH:32][CH2:31][CH2:30][C:29]2[C:24]3[O:23][CH:22]=[C:21]([C:17]4[CH:16]=[C:15]5[C:20](=[CH:19][CH:18]=4)[N:12]([C:10](=[O:11])[CH2:9][C:3]4[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=4[F:1])[CH2:13][CH2:14]5)[C:25]=3[C:26]([NH2:43])=[N:27][CH:28]=2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66823788bis(1,1-dimethylethyl) {3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-[2-({[(phenylmethyl)oxy]carbonyl}amino)ethyl]furo[3,2-c]pyridin-4-yl}imidodicarbonate

Product 1

HCID 69939762phenylmethyl [2-(4-amino-3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-7-yl)ethyl]carbamateYield 85.3%

Procedure

A mixture of bis(1,1-dimethylethyl) {3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-[2-({[(phenylmethyl)oxy]carbonyl}amino)ethyl]furo[3,2-c]pyridin-4-yl}imidodicarbonate (149 mg, 0.190 mmol) and 4.0 M HCl in dioxane (2.0 mL, 8.00 mmol) was stirred at room temperature under Nitrogen for 4 hr. The crude reaction mixture was then concentrated in vacuo and azeotroped once with acetonitrile. The residue was taken up in DCM and passed through a PL-HCO3 MP-resin cartridge, rinsing with more DCM. The filtrate was then concentrated in vacuo to give the free base of phenylmethyl[2-(4-amino-3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-7-yl)ethyl]carbamate (105 mg, 0.162 mmol, 85% yield) as an off-white foam (purity estimated at 90%). LC/MS (ES) m/z=583.6 [M+H]+. 1H NMR (400 MHz, DMSO-d6) d 2.86 (t, J=7.07 Hz, 2H), 3.22-3.34 (m, 4H), 3.96 (s, 2H), 4.31 (t, J=8.34 Hz, 2H), 5.02 (s, 2H), 5.38 (s, 2H), 7.14-7.44 (m, 12H), 7.68 (s, 1H), 7.93 (s, 1H), 8.12 (d, J=8.34 Hz, 1H).

Workup

  1. customThe crude reaction mixture
  2. concentrationwas then concentrated in vacuo
  3. customazeotroped once with acetonitrile
  4. washrinsing with more DCM
  5. concentrationThe filtrate was then concentrated in vacuo

Sources & evidence

ORD record
ord-2fab4b7a7fbd4f66b994c35599d0d281
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Linked notes

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